Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][CH:8]=[CH:7][C:6]=2[CH:10]=1.CN(C)CCN(C)C.[Li]CCCC.[B:24](OC(C)C)([O:29]C(C)C)[O:25]C(C)C>O1CCCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([B:24]([OH:29])[OH:25])=[CH:7][C:6]=2[CH:10]=1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Reactant: Fc1ccc2occc2c1
Agent: CN(C)CCN(C)C
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: OB(O)c1cc2cc(F)ccc2o1
Temperature: -10 °C
Reaction time: 0.5 h
Yield: 26.5 %

Procedure:
To a solution of 5-fluorobenzofuran (10 g, 73.53 mmol) in dry tetrahydrofuran (250 mL) were added tetramethylethylenediamine (10.2 g, 87.93 mmol). The solution was kept below −60° C. under nitrogen, while BuLi (93.75 mmol, 2.5M solution in hexane) was added dropwise. It was warmed to −10° C. during 45 min and stirred at this temperature for another 30 min. The mixture was cooled again below −60° C. followed by dropwise addition of triisopropyl borate (41.4 g, 220.21 mmol). After warming to room temperature the mixture was quenched with hydrochloric acid (70 mL, 2N) and stirred for 1 h. The alkaline aqueous layer was brought to pH 5 and extracted with ethyl acetate (3×80 mL). All organic layers were combined, dried over sodium sulfate, and concentrated in vacuo to give 5-fluorobenzofuran-2-ylboronic acid (3.5 g, 26%) which was used for the next step without further purification.
Reaction SMILES: C([O:5][C:6](=[O:31])[C:7]1[CH:12]=[CH:11][C:10]([N:13]([S:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)(=[O:24])=[O:23])[CH2:14][C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)=[CH:9][CH:8]=1)(C)(C)C>FC(F)(F)C(O)=O.ClCCl>[C:25]1([S:22]([N:13]([CH2:14][C:15]2[CH:16]=[CH:17][C:18]([Cl:21])=[CH:19][CH:20]=2)[C:10]2[CH:11]=[CH:12][C:7]([C:6]([OH:31])=[O:5])=[CH:8][CH:9]=2)(=[O:24])=[O:23])[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1
Reactant: CC(C)(C)OC(=O)c1ccc(N(Cc2ccc(Cl)cc2)S(=O)(=O)c2ccccc2)cc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C(O)c1ccc(N(Cc2ccc(Cl)cc2)S(=O)(=O)c2ccccc2)cc1
Yield: 62.2 %

Procedure:
A solution of 4-[benzenesulfonyl-(4-chloro-benzyl)-amino]-benzoic acid tert-butyl ester (2.1 g, 4.4 mmol) in 10% trifluoroacetic acid/dichloromethane (50 mL) was stirred at room temperature for 16 hours. The reaction mixture was concentrated in vacuo and the residue partitioned between sodium hydrogen carbonate (saturated solution, 25 mL) and dichloromethane (20 mL). The aqueous layer was separated, acidified (pH 1) using 10% HCl (aq) and the resulting solution extracted with dichloromethane (3×75 mL). The organics were combined, dried over magnesium sulfate and concentrated in vacuo to afford the title compound as a white solid (1.1 g, 62% yield)
Reaction SMILES: Cl[C:2]1[C:3](=[O:15])[N:4](C2CCCCO2)[N:5]=[CH:6][C:7]=1Cl.[OH:16][C:17]1[C:22](=[O:23])[CH:21]=[CH:20][O:19][C:18]=1[CH3:24].C[O:26][C:27](=[O:36])[CH:28](Br)[CH2:29][CH:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1>>[CH:30]1([CH2:29][CH:28]([N:4]2[C:3](=[O:15])[CH:2]=[C:7]([O:16][C:17]3[C:22](=[O:23])[CH:21]=[CH:20][O:19][C:18]=3[CH3:24])[CH:6]=[N:5]2)[C:27]([OH:26])=[O:36])[CH2:34][CH2:33][CH2:32][CH2:31]1
Reactant: COC(=O)C(Br)CC1CCCC1
Reactant: Cc1occc(=O)c1O
Reactant: O=c1c(Cl)c(Cl)cnn1C1CCCCO1
Product: Cc1occc(=O)c1Oc1cnn(C(CC2CCCC2)C(=O)O)c(=O)c1

Procedure:
In an analogous manner to the stepwise sequence outlined in intermediate 19, starting from 4,5-dichloro-2-(tetrahydropyran-2-yl)-2H-pyridazin-3-one (Intermediate 20) and 3-hydroxy-2-methyl-pyran-4-one and alkylating with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10) afforded 3-cyclopentyl-2-[4-(2-methyl-4-oxo-4H-pyran-3-yloxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid as a white solid (3.4 g, 30% for the final step); LC-MS: 361.1 [M+1]+ tR=3.10 min. Purity on HPLC: 97.7% (214 nm), 99.0% (254 nm), tR=5.79 min. 1H NMR (300 MHz, CDCl3): δ 7.97 (s, 1H), 7.86 (d, 1H, J=5.4 Hz), 6.59 (d, 1H, J=5.4 Hz), 6.15 (s, 1H), 5.57 (dd, 1H, J1=10.5 Hz, J2=4.5 Hz), 2.42 (s, 3H), 2.36˜2.23 (m, 1H), 2.23˜2.16 (m, 1H), 1.81˜1.57 (m, 7H), 1.32˜1.20 (m, 2H).
Reaction SMILES: [C:1]([C@@H:4]1[CH2:9][C@H:8]([N:10]([C:15]([C:17]2[N:21]([CH2:22][CH2:23][CH2:24][CH2:25][O:26][CH3:27])[C:20]3[CH:28]=[CH:29][CH:30]=[CH:31][C:19]=3[N:18]=2)=[O:16])[CH2:11][CH:12]([CH3:14])[CH3:13])[CH2:7][N:6]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:5]1)(=O)[NH2:2].FC(F)(F)C(OC(=O)C(F)(F)F)=O>N1C=CC=CC=1>[C:1]([C@@H:4]1[CH2:9][C@H:8]([N:10]([C:15]([C:17]2[N:21]([CH2:22][CH2:23][CH2:24][CH2:25][O:26][CH3:27])[C:20]3[CH:28]=[CH:29][CH:30]=[CH:31][C:19]=3[N:18]=2)=[O:16])[CH2:11][CH:12]([CH3:13])[CH3:14])[CH2:7][N:6]([C:32]([O:34][C:35]([CH3:37])([CH3:36])[CH3:38])=[O:33])[CH2:5]1)#[N:2]
Reactant: COCCCCn1c(C(=O)N(CC(C)C)[C@H]2C[C@@H](C(N)=O)CN(C(=O)OC(C)(C)C)C2)nc2ccccc21
Solvent: c1ccncc1
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Product: COCCCCn1c(C(=O)N(CC(C)C)[C@H]2C[C@@H](C#N)CN(C(=O)OC(C)(C)C)C2)nc2ccccc21
Temperature: 25 °C
Reaction time: 2 h
Yield: 103.5 %

Procedure:
tert-Butyl (3R,5S)-3-carbamoyl-5-{{{1-(4-methoxybutyl)-1H-benzimidazol-2-yl}carbonyl}(2-methylpropyl)amino}piperidine-1-carboxylate (1.01 g) was dissolved in pyridine (10 ml), trifluoroacetic anhydride (570 μl) was added at 0° C., and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure, and diluted with ethyl acetate. 1M Hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, and a fraction eluted with ethyl acetate-hexane (5:95)-ethyl acetate was concentrated under reduced pressure to give the object product (1.01 g).
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:28][Si:29]([CH3:37])([CH3:36])[C:30]#[C:31]/[CH:32]=[CH:33]/[CH2:34]O>ClCCl>[Br:1][CH2:34][CH:33]=[CH:32][C:31]#[C:30][Si:29]([CH3:37])([CH3:36])[CH3:28]
Reactant: C[Si](C)(C)C#C/C=C/CO
Reactant: O=C1CCC(=O)N1Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: C[Si](C)(C)C#CC=CCBr
Temperature: 25 °C
Reaction time: 2 h
Yield: 43.1 %

Procedure:
N-Bromosuccinimide (85.3 g, 0.48 mol) was added in portions to a nearly homogeneous solution of triphenylphosphine (128.2 g, 0.49 mol) and 2E-5-trimethylsilylpent-2-en-4-yn-1-ol (72.5 g, 0.47 mol) in dichloromethane (600 mL) under nitrogen and cooled in a dry ice/2-propanol bath to an initial temperature of below −20° C. The internal temperature of the reaction mixture was maintained at −10° C. to 0° C. throughout the addition by adjusting the rate of addition. The bath was allowed to warm to ambient temperature. After 2 hours, the reaction was complete. The reaction mixture was concentrated under vacuum to a thick paste and the residue was triturated with hexane (250 mL). The suspension was filtered and the solids and silica gel were rinsed with hexane (10×150 mL). The filtrate was concentrated under vacuum (30° C./60 mtorr) to obtain 44 g (89% yield) of 1-bromo-5-trimethylsilylpent-2-en-4-yne, a compound of formula (P), as a pale yellow oil: 1H-NMR (300 mHz, CDCl3) δ 0.19 (s, 9H), 3.95 (d, 2H), 5.75 (d, 1H), 6.31 (dt, 1H) ppm.
Reaction SMILES: [CH3:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([N+:9]([O-:11])=[O:10])[CH:3]=1.[CH:12](O)=[O:13].C(OC(=O)C)(=O)C>C(Cl)Cl>[CH3:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][CH:12]=[O:13])=[C:4]([N+:9]([O-:11])=[O:10])[CH:3]=1
Reactant: Cc1ccc(N)c([N+](=O)[O-])c1
Reactant: O=CO
Solvent: ClCCl
Solvent: CC(=O)OC(C)=O
Product: Cc1ccc(NC=O)c([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 97.7 %

Procedure:
4-Methyl-2-nitroaniline, 30 g (197 mmols), was dissolved in 500 ml of methylene chloride and a liquid mixture of 52 ml (1.378 mol) of formic acid and 31 ml (328 mmols) of acetic anhydride was added dropwise to the solution. The mixture was stirred at room temperature for 16 hours. The solvent was distilled off under reduced pressure. The resulting crystals were washed with ether to give 34.7 g (97.7%) of N-(4-methyl-2-nitrophenyl)formamide.
Reaction SMILES: C1C2C(=CC=CC=2)C=CC=1.C=CC=C.[CH2:15]1[C:28]2[C:27](=[O:29])[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20](=[O:30])[C:19]=2[CH2:18][CH2:17][CH2:16]1>>[CH:22]1[C:21]2[C:20](=[O:30])[C:19]3[C:28](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:27](=[O:29])[C:26]=2[CH:25]=[CH:24][CH:23]=1
Reactant: O=C1C2=C(CCCC2)C(=O)c2ccccc21
Agent: C=CC=C
Solvent: c1ccc2ccccc2c1
Product: O=C1c2ccccc2C(=O)c2ccccc21

Procedure:
Provided that volatile or gaseous compounds are used as the compounds with an alkaline reaction, these compounds can be added at one or more points between the reactor in which naphthalene is oxidised and the reactor in which the reaction with butadiene takes place, or into one or more of the gas streams which are recycled to the naphthalene oxidation. For example, volatile or gaseous compounds with an alkaline reaction can be added at the following points: between the reactor in which naphthalene is oxidised and the quenching and/or cooling device, into the quenching and/or cooling device, between the quenching and/or cooling device and the reactor in which the reaction with butadiene takes place, into the reactor in which the reaction with butadiene takes place, into the gases which are recycled from the quenching and/or cooling to the naphthalene oxidation or into the gases which are recycled to the naphthalene oxidation from the oxidation of tetrahydroanthraquinone to give anthraquinone. If non-volatile compounds with an alkaline reaction are used, it is appropriate to add the latter at points at which a liquid product is present, is conveyed or is formed immediately after the addition of the compound with an alkaline reaction. For example, non-volatile compounds with an alkaline reaction can be added at the following points: shortly before or at the entry of the gases from the naphthalene oxidation into the quenching and/or cooling device, into the quenching and/or cooling device, between the quenching and/or cooling device and the reactor in which the reaction with butadiene takes place, or into the reactor in which the reaction with butadiene takes place.
Reaction SMILES: [CH:1]1([NH:4][C:5](=[O:32])[C:6]2[CH:11]=[CH:10][C:9]([C:12]3[N:16]4[N:17]=[C:18]([O:23][C:24]5[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=5)[CH:19]=[C:20](SC)[C:15]4=[N:14][CH:13]=3)=[CH:8][C:7]=2[CH3:31])[CH2:3][CH2:2]1.O[O:34][S:35]([O-:37])=O.[K+].[CH3:39]N(C=O)C>>[CH:1]1([NH:4][C:5](=[O:32])[C:6]2[CH:11]=[CH:10][C:9]([C:12]3[N:16]4[N:17]=[C:18]([O:23][C:24]5[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=5)[CH:19]=[C:20]([S:35]([CH3:39])(=[O:37])=[O:34])[C:15]4=[N:14][CH:13]=3)=[CH:8][C:7]=2[CH3:31])[CH2:2][CH2:3]1
Reactant: CSc1cc(Oc2cccc(F)c2)nn2c(-c3ccc(C(=O)NC4CC4)c(C)c3)cnc12
Reactant: O=S([O-])OO
Reactant: CN(C)C=O
Agent: [K+]
Product: Cc1cc(-c2cnc3c(S(C)(=O)=O)cc(Oc4cccc(F)c4)nn23)ccc1C(=O)NC1CC1
Temperature: 70 °C
Yield: 93 %

Procedure:
To a stirred solution of 4.96 g (11.06 mmol) N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-(methylsulfanyl)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide which was prepared according to intermediate example 486b in DMF (250 mL) were added 20.4 g (33.18 mmol) oxone in one portion at rt. After reaction for 72 h, further 30 g (55 mmol) oxone are added and the mixture is heated at 70° C. for one hour. Extraction with ethyl acetate/water, filtration of the organic phase through a Whatman filter and evaporation of the organic phase yielded the crude product (4.96 g, 93%) which was used without further purification.
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[O:5]1[CH:9]=[CH:8][CH2:7][CH2:6]1>C(Cl)Cl>[C:1]([C:7]1[CH:8]=[CH:9][C:6]2[O:5][CH2:9][CH2:8][C:7]=2[CH:6]=1)(=[O:3])[CH3:2]
Reactant: C1=COCC1
Reactant: CC(=O)Cl
Solvent: ClCCl
Product: CC(=O)c1ccc2c(c1)CCO2
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 186.7 %

Procedure:
To a 0° C. solution of acetyl chloride (1.64 mL, 23.0 mmol, 1.3 equivalents) in methylene chloride (30 mL) was added stannic chloride (2.49 mL, 21.3 mmol, 1.2 equivalents), maintaining the temperature below 5° C. The solution was stirred 15 minutes at 0° C., and then a solution of 2,3-dihydrofuran (2.00 mL, 17.7 mmol) in methylene chloride (5 mL) was added dropwise while maintaining the temperature below 8° C. The dark red solution was stirred 1 hour at 2° C. and then poured into 50 mL of ice water. The reaction was stirred an additional 30 minutes, and the layers were separated. The organic layer was washed with water and aqueous sodium bicarbonate, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on 150 g silica gel, eluting with 18% ethyl acetate in hexanes. The solvents were removed under reduced pressure to yield the title compound (2.68 g, 93%) as a yellow solid.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH3:11][C:12]([CH3:27])([CH2:25][OH:26])[C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=1)=[O:14].CCN(C(C)C)C(C)C>C(Cl)Cl>[CH:25]([C:12]([CH3:27])([CH3:11])[C:13]([O:15][CH2:16][C:17]1[CH:18]=[CH:19][C:20]([O:23][CH3:24])=[CH:21][CH:22]=1)=[O:14])=[O:26]
Reactant: COc1ccc(COC(=O)C(C)(C)CO)cc1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc(COC(=O)C(C)(C)C=O)cc1
Temperature: 0 °C
Reaction time: 0.08 h

Procedure:
A solution of 0.2 mL (2.2 mmol) of oxalyl chloride in 4 mL of CH2Cl2 at −78° C. was treated with 0.32 mL (4.5 mmol) of DMSO in 0.5 mL of CH2Cl2 maintaining the temperature at less than 60° C. The resulting mixture was stirred cold for 5 min. A solution of 211 mg (0.94 mmol) of 2,2-dimethyl-3-hydroxypropionic acid, para-methoxybenzyl ester (from Step A) in 1 mL of CH2Cl2 was added maintaining the temperature at less than −60° C. The resulting mixture was stirred cold for 15 min. The mixture was treated with 1.6 mL (9.1 mmol) of DIEA maintaining the temperature at less than −60° C. The reaction was warmed to 0° C., stirred for 30 min and quenched with H2O. The mixture was partitioned between 50 mL of CH2Cl2 and 50 mL of H2O and the layers were separated. The aqueous layer was extracted with 50 mL of CH1Cl2. The combined organic phases were washed with 100 mL of brine, dried over Na2SO4 and concentrated to afford the title compound which was used without further purification: RF: 0.43 (4:1 v/v hexanes/EtOAc); 1H-NMR (500 MHz) δ 1.35 (s, 6H), 3.81 (s, 3H), 5.12 (s, 2H), 6.89 (d, J=8.7, 2H), 7.27 (d, J=8.7, 2H), 9.66 (s, 1H).
Reaction SMILES: Br[C:2]1[N:7]=[C:6]([CH:8]([O:10][CH2:11][C:12]2([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH2:17][CH2:16][N:15](C(OC(C)(C)C)=O)[CH2:14][CH2:13]2)[CH3:9])[CH:5]=[C:4]([C:31]([F:34])([F:33])[F:32])[CH:3]=1.C[Si](C)(C)[C:37]([F:40])([F:39])[F:38].[F-].[K+].CN1CCCC1=O>CN(C)C=O.[Cu]I>[C:25]1([C:12]2([CH2:11][O:10][CH:8]([C:6]3[CH:5]=[C:4]([C:31]([F:34])([F:33])[F:32])[CH:3]=[C:2]([C:37]([F:40])([F:39])[F:38])[N:7]=3)[CH3:9])[CH2:13][CH2:14][NH:15][CH2:16][CH2:17]2)[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1
Reactant: C[Si](C)(C)C(F)(F)F
Reactant: CC(OCC1(c2ccccc2)CCN(C(=O)OC(C)(C)C)CC1)c1cc(C(F)(F)F)cc(Br)n1
Agent: [Cu]I
Agent: [F-]
Agent: [K+]
Solvent: CN1CCCC1=O
Solvent: CN(C)C=O
Product: CC(OCC1(c2ccccc2)CCNCC1)c1cc(C(F)(F)F)cc(C(F)(F)F)n1
Temperature: 110 °C
Yield: 18 %

Procedure:
Tert-butyl 4-((1-(6-bromo-4-(trifluoromethyl)pyridin-2-yl)ethoxy)methyl)-4-phenylpiperidine-1-carboxylate (100 mg, 0.18 mmol), trimethyl(trifluoromethyl)silane (70 mg, 0.46 mmol), potassium fluoride (70 mg, 1.2 mmol) and Copper(I) Iodide (100 mg, 0.525 mmol) were combined in dry dimethylformamide (1 mL) and dry N-Methyl-2-pyrrolidinone (1 mL) in a sealed tube. The mixture was heated to 110° C. for 2 hours. After cooling the reaction mixture was quenched with the addition of ammonia hydroxide (6M, 15 mL). The reaction was diluted with ether, washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The resulting oil was redissolved in methanol (2 mL) and treated with HCl (g) for 30 seconds. The solvent was evaporated and preparatory HPLC afforded 14 mg (15%) of desired product as the TFA salt. 1H-NMR (CD3OD, 400 MHz) δ 7.92 (s, 1H), 7.24-7.57 (m, 6H), 4.54 (q, 1H), 3.91 (d, 1H), 3.57 (m, 1H), 2.82-3.03 (m, 2H), 2.51-2.77 (m, 2H), 2.34-2.48 (m, 2H), 2.03-2.22 (m, 2H), 1.38 (d, 3H). LC: Tr=1.785 min, HPLC Method 1. Mass spec.: 433.35 (MH)+.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[NH2:11])[C:5]([OH:7])=[O:6].S(=O)(=O)(O)O.[CH2:17](O)[CH3:18]>>[CH2:17]([O:6][C:5](=[O:7])[C:4]1[CH:8]=[CH:9][C:10]([NH2:11])=[C:2]([NH2:1])[CH:3]=1)[CH3:18]
Reactant: Nc1ccc(C(=O)O)cc1N
Reactant: CCO
Agent: O=S(=O)(O)O
Product: CCOC(=O)c1ccc(N)c(N)c1
Temperature: 25 °C
Yield: 90.4 %

Procedure:
76 g of 3,4-diaminobenzoic acid (0.5 mol) and 300 mL anhydrous ethyl alcohol were added to a three-necked bottle, to which 6 mL concentrated sulphuric acid was added slowly under stirring at room temperature. After refluxing for 3 h, the reaction was completed. After concentration under reduced pressure, the residual solution was poured into ice water. The resulting mixture was adjusted to pH 7 with saturated sodium carbonate aqueous solution. After sucking filtration and drying, 81.5 g solid was obtained. Yield: 90.4%. MS: 181(M+1).
Reaction SMILES: O.[CH3:2][C:3]1[CH:4]=[CH:5][C:6]([CH3:9])=[CH:7][CH:8]=1.[C:10]1(C)C=CC=CC=1>>[CH2:2]([C:3]1[CH:8]=[CH:7][C:6]([CH3:9])=[CH:5][CH:4]=1)[CH3:10]
Reactant: Cc1ccc(C)cc1
Reactant: Cc1ccccc1
Solvent: O
Product: CCc1ccc(C)cc1
Temperature: 90 °C
Reaction time: 14 h
Yield: 88.7 %

Procedure:
The same Ca-P-ZSM-5 catalyst is then treated with a stream of air which is first moistened with water at ambient temperature and is then passed for 14 hours at the rate of 300 cc/minute into the catalyst bed maintained at 90° C. After calcination at 500° C. for 1 hour, disproportionation and ethylation of toluene are again carried out under the same conditions used with the untreated catalyst. Toluene disproportionation gives 12.6% toluene conversion with a para-selectivity of 66.3% p-xylene in xylenes. Toluene ethylation gives 19.1% conversion of toluene with a para-selectivity of 88.7% p-ethyltoluene in ethyltoluenes.
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH3:11])[C:5]([OH:7])=O.CN(C(ON1N=NC2[CH:23]=[CH:24][CH:25]=[N:26]C1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.C1(N)CC1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH:25]1([NH:26][C:5](=[O:7])[C:4]2[CH:8]=[CH:9][C:10]([CH3:11])=[C:2]([I:1])[CH:3]=2)[CH2:23][CH2:24]1
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Reactant: Cc1ccc(C(=O)O)cc1I
Agent: F[P-](F)(F)(F)(F)F
Agent: NC1CC1
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccc(C(=O)NC2CC2)cc1I
Reaction time: 18 h
Yield: 81.7 %

Procedure:
3-Iodo-4-methylbenzoic acid (5 g, 19.1 mmol) and HATU (8.71 g, 22.9 mmol) in DMF (25 ml) were stirred at room temperature for 10 minutes. HOBT (2.58 g, 19.1 mmol), cyclopropylamine (1.37 g, 22.9 mmol) and DIPEA (2.5 ml, 57.3 mmol) were added and stirring continued for 18 h. The DMF was evaporated under vacuum and the residue partitioned between DCM (100 ml) and aqueous sodium carbonate (1M, 75 ml). The aqueous layer was extracted with DCM (50 ml) and the combined organic phases washed with brine (75 ml) and dried (magnesium sulphate). The solution was absorbed onto silica and purified by chromatography on silica eluting with ethyl acetate/cyclohexane (1:3). The product fractions were reduced to dryness under vacuum to give N-cyclopropyl-3-iodo-4-methylbenzamide (4.7 g, 82%). LCMS: retention time 3.09 min, MH+302.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[S:11][C:12]([CH2:15]O)=[CH:13][N:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:17]1(=[O:27])[NH:21][C:20](=[O:22])[C:19]2=[CH:23][CH:24]=[CH:25][CH:26]=[C:18]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[S:11][C:12]([CH2:15][N:21]2[C:20](=[O:22])[C:19]3=[CH:23][CH:24]=[CH:25][CH:26]=[C:18]3[C:17]2=[O:27])=[CH:13][N:14]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: CC(C)(C)OC(=O)NCc1ncc(CO)s1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NCc1ncc(CN2C(=O)c3ccccc3C2=O)s1
Temperature: 25 °C
Reaction time: 1 h
Yield: 63 %

Procedure:
To 20 ml of a THF solution containing 1.06 g of 2-(N-t-butoxycarbonylamino)methyl-5-hydroxymethylthiazole, 959 mg of phthalimide, 1.7 g of triphenylphosphine and 1.03 ml of diethyl azodicarboxylate were added, and the mixture was then stirred at room temperature for 1 hour. Then, the solvent was evaporated under reduced pressure, and the resulting residue was purified by a silica gel column chromatograph and Cephadex LH-20 in succession to obtain 1.02 g of 2-(N-t-butoxycarbonylamino)methyl-5-phthalimidomethylthiazole.
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:10][C:11]1[CH:12]=[C:13]([C:18]([NH:21][CH2:22][CH2:23][CH2:24][N:25]2[CH:29]=[CH:28][N:27]=[CH:26]2)([CH3:20])[CH3:19])[CH:14]=[CH:15][C:16]=1[Cl:17].Cl>ClCCl.C(N(CC)CC)C>[Cl:17][C:16]1[CH:15]=[CH:14][C:13]([C:18]([NH:21][CH2:22][CH2:23][CH2:24][N:25]2[CH:29]=[CH:28][N:27]=[CH:26]2)([CH3:19])[CH3:20])=[CH:12][C:11]=1[NH:10][C:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: CC(C)(NCCCn1ccnc1)c1ccc(Cl)c(N)c1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(NCCCn1ccnc1)c1ccc(Cl)c(NC(=O)c2ccccc2)c1
Temperature: 0 °C
Reaction time: 18 h

Procedure:
Benzoyl chloride (0.21 ml) was added to a solution of N-[1-(3-amino-4-chlorophenyl)-1-methylethyl]-3-(imidazol-1-yl)propylamine (0.50 g) in dichloromethane (50 ml) and triethylamine (0.25 ml) with stirring at 0° C. The mixture was allowed to warm up to ambient temperature and stirred at this temperature for 18 hours. The mixture was washed with water, dried and evaporated. The residue was purified by flash column chromatography on silica using ethyl acetate/methanol/triethylamine (8:1:1) as the mobile phase. The product was obtained as an oil which was added to ethereal hydrogen chloride to produce a gum. The gum was triturated and then left standing for 18 hours. The resulting solid was ground up, filtered and dried to give 2′-chloro-5′-{1-[3-(imidazol-1-yl)propylamino]-1-methylethyl}benzanilide.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][OH:5].C(N(CC)CC)C.[C:13]1([CH3:23])[CH:18]=[CH:17][C:16]([S:19](Cl)(=[O:21])=[O:20])=[CH:15][CH:14]=1.C(Cl)(Cl)Cl>ClCCl>[S:19]([C:16]1[CH:17]=[CH:18][C:13]([CH3:23])=[CH:14][CH:15]=1)([O:5][CH2:4][CH2:3][O:2][CH3:1])(=[O:21])=[O:20]
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: COCCO
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Product: COCCOS(=O)(=O)c1ccc(C)cc1
Temperature: 0 °C
Reaction time: 8 h
Yield: 92.5 %

Procedure:
2-methoxyethanol (0.989 g, 13 mmol) was dissolved in 30 ml dichloromethane, and triethylamine (2.53 g, 25 mmol) was added to the solution. The reaction mixture was set to stir in an ice-water bath, and p-toluenesulfonyl chloride (3.22 g, 17 mmol) was added all at once. The ice was allowed to melt, and the reaction was continued overnight. The reaction mixture was then filtered, to remove all of the triethylamine hydrochloride, and the filtrate was washed with ml saturated NaHCO3(aq), then 30 ml 1N KHSO4(aq), then 30 ml saturated NaHCO3(aq). The organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed by distillation. The colorless oily residue was chromatographed on silica gel in 1:5 ethyl acetate:chloroform, to yield 2.77 g (92% yield) of 2-methoxyethyl tosylate as a viscous liquid.